Diisopropylethylamine → N-[3-(3-{[5-(4-fluorophenyl)thieno[2,3-d]pyrimidin-4-yl]amino}propoxy)phenyl]acetamide

HRID 2102364Notes

Reaction equation

HRID 2102364 reaction equation
Cl[C:2]1[C:3]2[C:10]([C:11]3[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=3)=[CH:9][S:8][C:4]=2[N:5]=[CH:6][N:7]=1.[NH2:18][CH2:19][CH2:20][CH2:21][O:22][C:23]1[CH:24]=[C:25]([NH:29][C:30](=[O:32])[CH3:31])[CH:26]=[CH:27][CH:28]=1.C(N(C(C)C)CC)(C)C>CN(C)C=O>[F:17][C:14]1[CH:15]=[CH:16][C:11]([C:10]2[C:3]3[C:2]([NH:18][CH2:19][CH2:20][CH2:21][O:22][C:23]4[CH:24]=[C:25]([NH:29][C:30](=[O:32])[CH3:31])[CH:26]=[CH:27][CH:28]=4)=[N:7][CH:6]=[N:5][C:4]=3[S:8][CH:9]=2)=[CH:12][CH:13]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 2735413N-[3-(3-aminopropoxy)phenyl]acetamideHCID 27829114-Chloro-5-(4-fluorophenyl)thieno(2,3-d)pyrimidine

Product 1

HCID 11697822N-[3-(3-{[5-(4-fluorophenyl)thieno[2,3-d]pyrimidin-4-yl]amino}propoxy)phenyl]acetamideYield 75.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of 4-chloro-5-(4-fluorophenyl)thieno[2,3-d]pyrimidine (100 mg, 0.378 mmol), N-[3-(3-amino-propoxy)-phenyl]-acetamide (94 mg, 0.45 mmol), diisopropylethylamine (147 mg, 1.14 mmol) and N,N-dimethylformamide (3.0 mL) was warmed to 120° C. for 20 minutes by microwave irradiation. The solvent was then concentrated in vacuo and the residue was dissolved in ethyl acetate (50 mL) and washed with of aqueous sodium bicarbonate (2×30 mL). The organic layer was concentrated in vacuo and purified by column chromatography over silica gel using 1% methanol in dichloromethane as eluant to give 125 mg (73%) of N-[3-(3-{[5-(4-fluorophenyl)thieno[2,3-d]pyrimidin-4-yl]amino}propoxy)phenyl]acetamide as a white solid. MS [M+H] 437.1, 1H NMR (CDCl3) 6 (ppm) 8.50 (s, 1H), 7.41-7.36 (m, 2H), 7.25 (s, 1H), 7.21 (t, J=8.1 Hz, 1H), 7.07-6.95 (m, 3H), 6.94 (d, J=8.1 Hz, 1H), 6.55 (d, J=8.4 Hz, 1H), 5.01 (b, 1H), 3.89 (t, J=6.0 Hz, 2H), 3.64 (m, 2H), 2.19 (s, 3H), 1.98 (m, 2H).

Workup

  1. concentrationThe solvent was then concentrated in vacuo
  2. dissolutionthe residue was dissolved in ethyl acetate (50 mL)
  3. washwashed with of aqueous sodium bicarbonate (2×30 mL)
  4. concentrationThe organic layer was concentrated in vacuo
  5. custompurified by column chromatography over silica gel using 1% methanol in dichloromethane as eluant

Sources & evidence

ORD record
ord-04ebc39176d94d2c8f0c7189ac669905
Source dataset
uspto-grants-2009_08
Patent number
US07576080B2

Reaction notes

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